Clinical Theragnostic Relationship between Drug-Resistance Specific miRNA Expressions, Chemotherapeutic Resistance, and Sensitivity in Breast Cancer: A Systematic Review and Meta-Analysis.

Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran's Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger's bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508-1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.

Epidemiologic analysis of breast cancer incidence, prevalence, and mortality in India: Protocol for a systematic review and meta-analyses.

BACKGROUND: Breast Cancer (BC) is the leading cause of deaths in Indian women. Emerging reports reveal alarming evidence of increasing incidence and mortality of BC among young Indian women in addition to the late presentation and poor prognosis. Despite the significant incidence, there is a lack of reliable data resources and comprehensive epidemiologic studies relating to BC. The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the incidence, prevalence, and mortality of BC in 29 states and seven union territories of India. METHODS: Data sources used will be Cochrane Review, MEDLINE, PubMed, Scopus, Science Direct, Web of Science, and international and national cancer registries such as World Health Organization, International Agency for Research on Cancer (IARC), and National Centre for Disease Information and Research (NCDIR)-National Cancer Registry Program initiated by Indian Council of Medical Research. Relevant data will be extracted using a predefined data collection form. A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies. This study protocol was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 guidelines. Odds ratios (ORs) will be used to measure effect size. The random or fixed-effects meta-analyses model will be employed to aggregate the pooled estimates (ORs) with 95% confidence intervals (CIs) separately. A forest plot will be produced to assess ORs and 95% CIs. Publication bias will be assessed using funnel plot, and Egger regression will be applied to test the symmetry of the funnel plot. ETHICS AND DISSEMINATION: This proposed study will be based on published studies and the data from cancer registries. Therefore, human research ethics approval is not required. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NO: CRD42018084003.